The rise and fall of long-latency Plasmodium vivax

Abstract

Until World War II the only clinical phenotype of Plasmodium vivax generally recognised in medicine was one associated with either a long (8-9 months) incubation period or a similarly long interval between initial illness and the first relapse. Long-latency P. vivax 'strains' were the first in which relapse, drug resistance and pre-erythrocytic development were described. They were the infections in which primaquine radical cure dosing was developed. A long-latency 'strain' was the first to be fully sequenced. Although long-latency P. vivax is still present in some parts of Asia, North Africa and the Americas, in recent years it has been largely forgotten.

Keywords: Plasmodium vivax; long latency; malaria; relapse.

Figure 1.

General temporal pattern of initial illness (light brown) and relapses (black) with different P. vivax phenotypes mainly characterized from volunteer/malariotherapy studies in which infections were usually with 5–10 infected mosquitoes (red arrow). Intervals are those associated with slowly eliminated antimalarial treatments (chloroquine, mepacrine, piperaquine). The light grey triangles depict relapses occurring in a minority of cases. Early relapse in long-latency P. vivax was more likely with heavy sporozoite inocula, although some strains never relapsed early (<2 months) in volunteer/malariotherapy studies.

Figure 2.

Relapse pattern following acute vivax malaria in Kolkata from Kim et al. The majority of relapses occurred within 100 d of the acute infection. Approximately half of these early recurrences were with parasites that were genetically related to the index infection, suggesting they arose from the same sporozoite inoculum (red line). The other half were genetically unrelated, suggesting activation of previously acquired hypnozoites or reinfection (grey line). There was a steady rate of reinfection throughout the year (dashed line). Beginning 8 months after the index infections, there were six temporally grouped genetically homologous relapses indicating the long-latency P. vivax phenotype. This suggests co-circulation of frequent-relapse (‘Chesson type’) and long-latency P. vivax parasites.